# High-Throughput Screening for the Discovery of Protein-Binding Fragments

> **NIH NIH R43** · DELUGE BIOTECHNOLOGIES, INC. · 2023 · $274,865

## Abstract

Project Summary
Fragment based drug discovery programs begin with the identification of low molecular
compounds that bind weakly to the protein of interest (POI). POI-binding fragments are
then elaborated and/or linked together to provide lead compounds. Current methods for
screening fragment libraries have low throughput and many require large amounts of the
POI, often in isotopically labeled form. This proposal will establish a novel screening
platform capable of analyzing hundreds of potential fragment-protein interactions in a
single tube. We will create dozens of fluorescently encoded one bead one compound
(OBOC) libraries comprised of hundreds of low molecular weight compounds. They will
be screened against a fluorescently labeled, tetrameric form of the POI. Avidity effects
will stabilize the weak interactions sufficiently to allow the beads to be analyzed by flow
cytometry, identifying those capable of retaining the POI. If necessary, proximity
labeling will be explored to increase the sensitivity of the system. This technology will be
employed to discover novel fragments that engage the VHL E3 Ubiquitin ligase.

## Key facts

- **NIH application ID:** 10759032
- **Project number:** 1R43GM151901-01
- **Recipient organization:** DELUGE BIOTECHNOLOGIES, INC.
- **Principal Investigator:** Weijun Gui
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $274,865
- **Award type:** 1
- **Project period:** 2023-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10759032

## Citation

> US National Institutes of Health, RePORTER application 10759032, High-Throughput Screening for the Discovery of Protein-Binding Fragments (1R43GM151901-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10759032. Licensed CC0.

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